Early-Life Factors Associated with Adult-Onset Type 1 Diabetes: A Swedish Nationwide Cohort and Family-Based Study

Objective Childhood-onset type 1 diabetes (T1D) is associated with perinatal factors, but data related to adult-onset T1D are scarce. This study aimed at investigating the association between early-life factors and adult-onset T1D in a Swedish nationwide cohort and family-based study. Research Design and Methods We included 1,813,415 individuals aged ≥18 years, born in Sweden 1983 to 2002, followed until 2020. T1D diagnosis (n= 3,283) was identified from the National Diabetes, Patient and Prescribed Drugs Registers, and perinatal exposures were obtained from the Medical Birth Register. We performed Cox proportional hazard (HR [95% CI]) regression with mutual adjustment for perinatal exposures, sex, birth year, and parental sociodemographic background and history of diabetes. We also compared T1D risks among siblings’ groups identified from the Multiple Generation Register. Results The incidence rate of adult-onset T1D was 18.8 per 100,000 person-years. Year of birth (1.06[1.01-1.10], per five additional years) and history of maternal (4.10[3.09-5.43]) and paternal (6.24[5.10-7.64]) T1D were associated with a higher incidence of adult-onset T1D, whereas female sex (0.69[0.64-0.74]) and having parents born outside Sweden were associated with a lower incidence. Regarding perinatal exposures, only non-full-term birth (< 39 weeks versus ≥ 39 weeks) was associated with a higher incidence of adult-onset T1D (1.12[1.04-1.22]). The sibling cohort results were consistent with the full cohort analysis. Conclusions Perinatal factors seem to play a minor role in the development of adult-onset T1D compared to childhood-onset T1D, suggesting that triggers or accelerators of autoimmunity occurring later in life are more significant.